PTF1A

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding	IBA GO_REF:0000033	ACCEPT	Summary: PTF1A is the sequence-specific bHLH DNA-binding subunit of the trimeric PTF1 transcription factor and recognizes the E-box component of composite PTF1 regulatory sites. Reason: This is a core activity and the phylogenetic inference is consistent with biochemical evidence that PTF1A functions in a stable trimeric DNA-binding complex. Supporting Evidence: PMID:17938243 stable trimeric DNA-binding complex (PTF1)
GO:0006357 regulation of transcription by RNA polymerase II	IBA GO_REF:0000033	ACCEPT	Summary: PTF1A-containing PTF1 complexes regulate RNA polymerase II transcription of lineage and differentiated-cell target genes. Reason: Regulation of RNA polymerase II transcription is the core process executed by the PTF1 transcription factor complex. Supporting Evidence: PMID:18606784 directs the transcriptional activation of the secretory digestive enzyme genes
GO:0032502 developmental process	IBA GO_REF:0000033	MODIFY	Summary: PTF1A has conserved developmental roles, but the root-level term does not identify any of the established tissue or lineage outputs. Reason: The annotation is biologically sound but too general. Pancreas development, cerebellum development, and regulation of neural retina development capture supported contexts more informatively. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002360678 · PTF1A family node SUPPORTS TRANSFER The family-level developmental inference is biologically sound, but the root developmental-process term is less informative than the established tissue contexts. Proposed replacements: pancreas development cerebellum development regulation of neural retina development
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: PTF1A is active in the nucleus as a DNA-binding subunit of the PTF1 transcription regulator complex. Reason: Nuclear activity is integral to PTF1A's core transcription-factor function and is supported by complex binding to target promoters.
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IBA GO_REF:0000033	ACCEPT	Summary: PTF1A is a bHLH DNA-binding transcription factor that regulates RNA polymerase II target genes within the PTF1 complex. Reason: This correctly captures the core molecular activity, although the activator-specific child GO:0001228 is still more informative for synthesis. Supporting Evidence: PMID:11318877 p48 stimulated transcription from the PTF1 motif synergistically with E47
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: Automated localization to the nucleus agrees with PTF1A's experimentally supported transcription-factor activity. Reason: The annotation is correct and independently consistent with the IBA nuclear activity annotation and promoter-bound PTF1 complexes.
GO:0005737 cytoplasm	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Cytoplasmic PTF1A has been described by similarity and in pathological pancreatic contexts, but it is not the site of productive PTF1 transcriptional activity. Reason: Retain the localization state while distinguishing it from the nuclear core function; cytoplasmic accumulation is associated with failure to form the PTF1 complex.
GO:0043565 sequence-specific DNA binding	IEA GO_REF:0000117	MODIFY	Summary: PTF1A binds DNA sequence-specifically through its bHLH domain, but this term omits its known E-box specificity. Reason: GO:0070888 E-box binding is a more informative description of the PTF1A bHLH DNA-recognition activity. Proposed replacements: E-box binding
GO:0046983 protein dimerization activity	IEA GO_REF:0000002	ACCEPT	Summary: PTF1A forms a bHLH heterodimer with a class A E protein as the DNA-binding portion of the trimeric PTF1 complex. Reason: Dimerization is a mechanistically necessary molecular activity and is more informative than generic protein binding. Supporting Evidence: PMID:16354684 It comprises a dimer of P48/PTF1a
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IEA GO_REF:0000107	ACCEPT	Summary: Orthology transfer of cis-regulatory-region binding is consistent with direct PTF1 binding at target promoters and enhancers. Reason: This accurately captures the regulatory DNA-binding activity of PTF1A and complements the IBA annotation to GO:0000977. Supporting Evidence: PMID:17938243 PTF1 complex containing RBPJ is bound to the Rbpjl promoter
GO:0003677 DNA binding	IEA GO_REF:0000120	MODIFY	Summary: PTF1A binds DNA, but the generic term loses its sequence and regulatory-context specificity. Reason: Replace generic DNA binding with E-box binding, which reflects the bHLH recognition mechanism. Proposed replacements: E-box binding
GO:0005667 transcription regulator complex	IEA GO_REF:0000107	ACCEPT	Summary: PTF1A is an active subunit of the trimeric PTF1 transcription regulator complex with an E protein and RBPJ or RBPJL. Reason: Complex membership is central to PTF1A function and is directly established biochemically. Supporting Evidence: PMID:16354684 PTF1 is a trimeric transcription factor
GO:0006355 regulation of DNA-templated transcription	IEA GO_REF:0000120	MODIFY	Summary: The annotation is correct but broader than the demonstrated activation of RNA polymerase II-dependent target genes. Reason: GO:0045944 specifies both the RNA polymerase and positive regulatory direction. Proposed replacements: positive regulation of transcription by RNA polymerase II
GO:0010842 retina layer formation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Mouse Ptf1a loss changes retinal horizontal, amacrine, and ganglion-cell production, supporting an effect on retinal-layer composition. Reason: The orthology-transferred developmental output is supported, but it is a tissue-specific consequence of PTF1A transcriptional activity rather than a core molecular function. Supporting Evidence: PMID:17075007 profound decrease of amacrine cells and an increase in ganglion cells
GO:0021549 cerebellum development	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: PTF1A specifies cerebellar ventricular-zone-derived inhibitory neuron lineages, including Purkinje cells and interneurons. Reason: The annotation is strongly supported by mouse genetics and human disease, but it is a tissue-specific developmental output of the core transcription-factor activity. Supporting Evidence: PMID:17360405 specification and normal production of PCs and cerebellar interneurons
GO:0030902 hindbrain development	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: PTF1A-dependent inhibitory-neuron specification occurs in the cerebellum and other dorsal hindbrain derivatives. Reason: This broad anatomical developmental term is plausible and conserved, but represents a contextual output rather than the gene product's core molecular activity.
GO:0031017 exocrine pancreas development	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: RBPJL-containing PTF1 complexes direct the differentiating and mature pancreatic acinar gene-expression program. Reason: Exocrine pancreas development is a well-supported tissue-specific output, not a separate molecular activity of PTF1A. Supporting Evidence: PMID:18606784 becomes restricted to the differentiating acinar cells
GO:0035881 amacrine cell differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ptf1a is required for normal amacrine-cell production and prevents a fate switch to retinal ganglion cells in mouse. Reason: The transferred annotation is biologically supported but describes a retinal lineage-specific output. Supporting Evidence: PMID:17075007 profound decrease of amacrine cells and an increase in ganglion cells
GO:0045893 positive regulation of DNA-templated transcription	IEA GO_REF:0000107	MODIFY	Summary: PTF1A-containing complexes activate transcription, but the term does not specify RNA polymerase II. Reason: GO:0045944 is the appropriate more specific term for the demonstrated transcriptional activation. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:11318877 p48 stimulated transcription from the PTF1 motif synergistically with E47
GO:0048384 retinoic acid receptor signaling pathway	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: The source mouse experiment reports induction of Ptf1a during retinoic-acid-driven neural commitment, placing Ptf1a downstream of the stimulus. Reason: Retinoic-acid responsiveness does not establish that PTF1A is itself a component of the retinoic acid receptor signaling pathway. The transfer reverses or overextends the causal relation supported by the accessible source. Supporting Evidence: PMID:11318877 expression of p48 was induced in P19 cells when they committed to neural fate upon retinoic acid treatment
GO:0048699 generation of neurons	IEA GO_REF:0000107	MODIFY	Summary: PTF1A controls inhibitory-neuron lineage specification rather than neuron generation generically. Reason: GO:0097154 GABAergic neuron differentiation captures the supported lineage direction and avoids implying an unrestricted neurogenic role. Proposed replacements: GABAergic neuron differentiation Supporting Evidence: PMID:18198335 required in vivo for specification of the GABAergic neurons
GO:0061074 regulation of neural retina development	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ptf1a directs horizontal and amacrine fate and suppresses ganglion-cell fate in the developing mouse retina. Reason: This is a supported retinal developmental role but remains a context-specific output of the core transcriptional activity.
GO:0031017 exocrine pancreas development	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Curator-reviewed orthology transfer of the established Ptf1a role in exocrine/acinar pancreatic differentiation. Reason: The inference is well supported across mammals; the process is a tissue-specific output rather than the core molecular function.
GO:0031017 exocrine pancreas development	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: The second curator-reviewed ISS row transfers the established exocrine-pancreas role from rat Ptf1a; it is distinct in GOA by its supporting ortholog even though its term, evidence code, and reference match the mouse-derived row. Reason: The rat ortholog supports the conserved pancreatic context. As with the mouse-derived ISS row, this developmental output is retained but is not the core molecular activity.
GO:1990837 sequence-specific double-stranded DNA binding	IDA PMID:28473536 Impact of cytosine methylation on DNA binding specificities ...	UNDECIDED	Summary: The cited methyl-SELEX study assayed hundreds of human transcription factors, but the cached full text does not expose a PTF1A-specific result or motif assignment. Reason: Sequence-specific DNA binding is fully consistent with PTF1A biology, so the annotation is not rejected. However, the PTF1A-specific experimental record cannot be verified from the accessible paper text or tables; curator evidence is therefore deferred rather than overruled. Supporting Evidence: PMID:28473536 By analysis of 542 human TFs with methylation-sensitive SELEX
GO:0000785 chromatin	ISA GO_REF:0000113	ACCEPT	Summary: PTF1A functions at cis-regulatory DNA in chromatin as a sequence-specific transcription factor. Reason: The TFClass-based inference is compatible with direct promoter occupancy by PTF1 complexes and the nuclear transcriptional role.
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	ISA GO_REF:0000113	ACCEPT	Summary: TFClass sequence- and architecture-based inference identifies PTF1A as a bHLH DNA-binding RNA polymerase II transcription factor. Reason: The inferred activity is strongly corroborated by biochemical studies of PTF1 complex binding and transcriptional activation.
GO:0010842 retina layer formation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Curator-reviewed transfer from mouse reflects the altered retinal cell composition produced by Ptf1a loss. Reason: The annotation is supported, but retina formation is a context-specific developmental output.
GO:0021549 cerebellum development	IMP PMID:15543146 Mutations in PTF1A cause pancreatic and cerebellar agenesis.	KEEP AS NON CORE	Summary: Human loss-of-function alleles cause cerebellar agenesis, and detailed Ptf1a-null mouse neuropathology confirms an essential cerebellar requirement. Reason: The experimental phenotype strongly supports the annotation. Cerebellum development is retained as a major tissue-specific output rather than the core molecular activity. Supporting Evidence: PMID:15543146 key regulator of cerebellar neurogenesis
GO:0031016 pancreas development	IMP PMID:15543146 Mutations in PTF1A cause pancreatic and cerebellar agenesis.	KEEP AS NON CORE	Summary: Biallelic PTF1A truncating variants cause pancreatic agenesis, establishing an essential role in human pancreatic development. Reason: The experimental disease genetics strongly supports the process annotation, which is a tissue-specific consequence of PTF1 complex activity. Supporting Evidence: PMID:15543146 Mutations in PTF1A cause pancreatic and cerebellar agenesis.
GO:0035881 amacrine cell differentiation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Curator-reviewed transfer from mouse is supported by loss of most amacrine cells and a retinal ganglion-cell fate switch after Ptf1a inactivation. Reason: The lineage role is conserved and supported, but it is a retinal context-specific output.
GO:0061074 regulation of neural retina development	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Curator-reviewed orthology transfer captures Ptf1a-dependent retinal progenitor fate allocation. Reason: The annotation is biologically well supported in mouse but represents a tissue-specific developmental output.
GO:0003677 DNA binding	ISS GO_REF:0000024	MODIFY	Summary: Orthology transfer correctly recognizes PTF1A as a DNA-binding protein, but the term is uninformatively broad. Reason: E-box binding is the appropriate specific replacement for the PTF1A bHLH subunit. Proposed replacements: E-box binding
GO:0005634 nucleus	ISS GO_REF:0000024	ACCEPT	Summary: Orthology-based nuclear localization is consistent with the conserved PTF1 complex and with direct occupancy of target regulatory DNA. Reason: Nuclear localization is the site of PTF1A's core transcriptional activity.
GO:0005667 transcription regulator complex	ISS GO_REF:0000024	ACCEPT	Summary: Orthology transfer of transcription-regulator-complex membership is directly corroborated by the conserved trimeric PTF1 complex. Reason: Complex membership is mechanistically central and supported by biochemical and genetic evidence.
GO:0005737 cytoplasm	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Cytoplasmic localization is transferred from rat and is consistent with a described nonproductive or pathological localization state. Reason: Retain the orthology-supported localization, but distinguish it from nuclear PTF1A activity; cytoplasmic PTF1A does not form the functional PTF1 complex.
GO:0006355 regulation of DNA-templated transcription	ISS GO_REF:0000024	MODIFY	Summary: The transferred process is correct but less precise than the demonstrated positive regulation of RNA polymerase II transcription. Reason: Replace it with GO:0045944 to capture both the activating direction and polymerase. Proposed replacements: positive regulation of transcription by RNA polymerase II
GO:0009888 tissue development	IDA PMID:12185368 The role of the transcriptional regulator Ptf1a in convertin...	MODIFY	Summary: The cited lineage-tracing and loss-of-function study specifically establishes Ptf1a's role in pancreatic fate acquisition, whereas tissue development is excessively broad. Reason: GO:0031016 pancreas development captures the experimentally demonstrated tissue context without generalizing to all tissue development. Proposed replacements: pancreas development Supporting Evidence: PMID:12185368 inactivation of Ptf1a switches the character of pancreatic progenitors
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific	ISS PMID:11318877 p48 subunit of mouse PTF1 binds to RBP-Jkappa/CBF-1, the int...	NEW	Summary: Proposed specific molecular-function annotation for PTF1A's sequence-specific transcriptional activation in the PTF1 complex. Reason: Ptf1a/E47 activates transcription from the composite PTF1 motif, and RBPJ further stimulates this activity. The human protein and its complex-forming interfaces are conserved; GO:0001228 captures the activity more precisely than the existing generic transcription-factor term. Supporting Evidence: PMID:11318877 p48 stimulated transcription from the PTF1 motif synergistically with E47

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

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